Although serum insulin-like growth factor I (IGF-I) concentrations have utility as a screening test for growth hormone (GH) deficiency in children and young adults, they are less accurate for screening in adults over 40 years of age. There are two main limitations in the clinical use of IGF-I levels as a marker of GH secretion. First, IGF-I synthesis is not only regulated by GH but also by nutrient supply and by other hormones; second, low IGF-I levels in the presence of normal or increased GH secretion may reflect a peripheral resistance to GH action. Although serum IGF-I cannot be used as a stand-alone test for the diagnosis of adult GH deficiency, very low IGF-I levels in the context of documented hypothalamic or pituitary disease may be helpful in identifying patients with a high probability of GH deficiency. In the presence of two or more additional pituitary hormone deficiencies, an IGF-I level <84 mug/l (assayed by Esoterix Endocrinology, Inc. Calabasas Hills, CA, USA) indicates a 99% probability of GH deficiency. As this cut-off value has not been validated for other IGF-I assays, an IGF-I standard deviation score (SDS) of <-3 may be considered in adults over age 28; an even lower IGF-I SDS is needed for diagnosis in younger adults. In clinical practice, other causes of low serum IGF-I such as malnutrition, diabetes, hypothyroidism, liver disease, etc., should be excluded before applying these diagnostic criteria.

The aim of our study was to evaluate the effects of long-life severe growth hormone deficiency on bone mineral density (BMD) and bone scintigraphy in adult patients with childhood onset (CO) hypopituitarism never treated with growth hormone. Our studies included 22 adult patients with CO hypopituitarism never treated with growth hormone (13 males and 9 females, aged 25-66 yr). The patients received replacement therapy with thyroxine, sex steroid hormones, and patients with secondary adrenocortical deficiency, hydrocortisone, but none of the patients had ever received GH treatment. In 22 patients, the total body with regional distribution of BMD, the lumbar spine L2-L4, and radial (33% site) BMD were determined by dual energy X-ray absorptiometry (DXA). In addition, 12 patients had the femoral neck BMD examined. In 10 cases, bone scintigraphy using 99-technetium labeled methylene diphosphonate was performed. Our studies revealed abnormalities, not yet described, in the regional distribution of BMD and bone scintigraphy in adults with CO hypopituitarism never treated with GH. In all patients, the results obtained from the total body showed definite disproportion in the regional distribution of BMD with a significantly advanced bone mineral deficit in the legs and a moderate deficit in the arms and total body. Local BMD measured at the radial (33% site) and lumbar spine L2-L4 revealed also a more pronounced bone mineral deficit in the cortical bone (33% distal radius) than in the trabecular bone (spine L2-L4). Bone scintigraphy showed a decrease in tracer accumulation in the shafts of the long bones but normal uptake in the spine, ribs, sternum, skull, and periarticular areas, indicating suppressed skeletal metabolism of cortical bone. Our studies indicate that long-life growth hormone deficiency leads to deficient and abnormal distribution of bone mineralization, a more pronounced deficit of BMD at the cortical bone, mainly expressed in the shafts of the long bones of the legs and arms, and moderately reduced BMD at the trabecular bone. Bone scans displaying low diphosphonates uptake in the shafts of the long bones point to greatly suppressed skeletal metabolism of the cortical bone in the patients with CO hypopituitarism never treated with GH.

In young male subjects peripherally administered growth hormone-releasing hormone (GHRH) enhances GH and slow wave sleep (SWS) and blunts cortisol. In contrast, in a sample of females 19-76-year old, GHRH impairs sleep and enhances adrenocorticotropic hormone (ACTH) and cortisol. In the latter study, the days of investigation were not adapted to the menstrual cycle and premenopausal and postmenopausal women as well were included. Placebo and GHRH were given during consecutive nights. In order to confirm or reject the sexual dimorphism of the effects of GHRH on sleep we applied an improved study design. In the present study we examined the effect of pulsatile administration of two dosages of GHRH (4×25 or 4x50mug intravenously, respectively) on sleep electroencephalogram (EEG) and nocturnal hormone secretion in healthy young women according to a randomized schedule. To rule out the influence of gonadal hormone activity, the study was adapted to the phase of the menstrual cycle and was performed at 4-6th day of menstrual cycle. A carry-over effect was excluded by the interval of at least 4 weeks between examinations. Compared to placebo rapid-eye-movement sleep decreased during the first half of the night after 4x25mug GHRH and sleep stage 4 decreased after 4x50mug GHRH. After both dosages GH increased whereas ACTH and cortisol remained unchanged. This study confirms that systemic GHRH impairs sleep in women.

Isolated growth hormone deficiency. Hernández LM, Lee PD, Camacho-Hübner C. Pituitary. 2007;10(4):351-7. Department of Endocrinology, William Harvey Research Institute, St. Bartholomew’s and the Royal London Hospitals, QM, University of London, London, UK.

Isolated growth hormone deficiency (IGHD) represents conditions of GH deficiency that are not necessarily associated with other pituitary hormone deficiencies or with an organic lesion. Three sub-categories of IGHD have been clinically identified (IGHD types 1-3), and IGHD type 1 has been further separated into IGHD types 1a and b. However, this clinical sub-categorization of IGHD may need reconsideration due to the recent identification of molecular heterogeneity within each sub-type of IGHD. In a small number of children with IGHD, defects in the GH, GH-releasing hormone receptor (GHRH-R), and GH1 genes have been identified. In most cases, no cause for IGHD can be identified; however, the proportion of idiopathic IGHD cases may be decreasing due to identification of causative factors. The phenotype of IGHD is variable depending in part on the underlying genetic disorders in the affected individuals. Several studies have focused on the usefulness of MRI findings in patients with GHD but anatomic abnormalities of the pituitary gland are variable. We review current studies and the clinical, biochemical, and molecular features described for different groups of affected individuals with IGHD.

The benefits of long-term effects of growth hormone (GH) substitution on carbohydrate and lipid metabolism in GH-deficient (GHD) adults are still controversial. The purpose of this study was to evaluate the effects of 5 years of GH substitution on body composition, glucose and lipid metabolism, and carotid artery intima-media thickness (IMT) in GHD adults. Fourteen patients were clinically assessed every 3 months for 5 years. Serum insulin-like growth factor 1 levels, lipid profile, oral glucose tolerance test, and ultrasonography of the carotid arteries were performed at baseline, 6 months, and every year during replacement. Visceral fat was measured by computed tomographic scan at baseline and at 6, 12, 24, and 60 months. The waist circumference was reduced after 6 months but increased during the next months toward baseline values. Visceral fat decreased during the study. Fasting glucose and insulin levels did not change, as well as the homeostasis model assessment of insulin resistance index. Despite an initial increase in frequency of abnormal glucose tolerance, mean 2-hour oral glucose tolerance test glucose levels decreased during the last 2 years. There was an increase in apolipoprotein A-1 levels during the treatment. Apolipoprotein B levels were reduced after 6 months and remained stable thereafter. A reduction in carotid artery IMT was observed during replacement. We concluded that 5 years of GH replacement therapy promoted positive effects on visceral fat, lipid profile, and carotid artery IMT in GHD adults. Long-term therapy improves insulin sensitivity through a reduction in visceral fat, and continuing monitoring is mandatory in terms of glucose metabolism.

Short stature and growth hormone deficiency (GHD) are frequent occurrences in thalassaemic children, while data on the prevalence of GHD in adult patients are lacking. Therefore, we elected to study the growth hormone and insulin-like growth factor-I (GH-IGF-I) axis in a large group of adult thalassaemic subjects. . . . Findings from this study demonstrate that GHD, either partial or severe, is not a rare occurrence in adult thalassaemic patients. GHD is associated with a higher prevalence of low serum IGF-I levels, recorded also in patients with normal GH secretion. The lack of correlation between ferritin and both GH peaks and IGF-I SDS suggests that mechanisms additional to iron overload, whose relevance cannot however be definitely ruled out, play a role in the pathophysiology of somatotrophin-somatomedin deficiency in this clinical condition. The positive correlation between IGF-I SDS on the one hand and GH peaks and pseudocholinesterase values on the other hand indicates that reduced liver protidosynthetic activity, in addition to somatotrophin secretory status, is a major determinant of the impaired IGF-I production in thalassaemia. Therefore biosynthetic GH replacement therapy in GH-deficient thalassaemic adults is worth considering.

GHD in adults is a recognised clinical entity. There is still, however, an ongoing debate of the clinical need and the importance of replacing GH in adults with severe GH deficiency. . . . AGHD is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein. . . . . In patients with lifetime isolated GHD, 6-month treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in intima-media thickness and in the number of atherosclerotic carotid plaques.

Several studies have demonstrated an improvement in aerobic exercise capacity with six months of GH replacement in adults with GH deficiency (GHD). Objective: To determine whether improvements in aerobic exercise capacity with GH treatment in adults with GHD are related to changes in physical activity or affected by the GH dosing regimen. . . .: GH replacement therapy in GH-deficient adults improved VO2 max similarly with both dosing regimens, without any influence of physical activity. There was no effect on submaximal exercise performance.